On the mechanism of the comutagenic effect of Cu(II) with ultraviolet light

Although CuCl2 alone is not mutagenic in E. coli or in Chinese hamster cells, exposure of E. coli to CuCl2 during UV-irradiation causes enhancement of UV-mutagenesis. The mechanism for this comutagenic effect appears to be owing to increased DNA damage by the combined treatment of UV and Cu(II) compared with UV or Cu(II) alone. Using a sequencing gel approach, UV alone is found to cause a particular pattern of alkali-labile sites, whereas CuCl2 alone caused few such sites. The combined action of UV + CuCl2 greatly increased the amount of sites over that of UV alone, and caused a change in their pattern. In the presence of high NaCl concentrations, however, Cu(II) is able to induce DNA damage. This latter effect is most likely owing to the formation of hypochlorite ion. The hypothesis that the comutagenic effect of Cu(II) plus UV might be owing to hydroxyl radical formed via a Fenton reaction involving Cu(II) and UV-generated H2O2 was not supported, since no H2O2 is detectable in aqueous medium after UV irradiation, and catalase did not block the DNA damage. These results favor the hypothesis that UV-irradiation of Cu(II) causes a photoactivation, enabling it to generate free radicals, perhaps by reacting with dissolved oxygen.